title: NG2 regulates directional migration of oligodendrocyte precursor cells via Rho GTPases and polarity complex proteins.
abstract: The transmembrane proteoglycan NG2 is expressed by oligodendrocyte precursor cells (OPC), which migrate to axons during developmental myelination and remyelinate in the adult after migration to injured sites. Highly invasive glial tumors also express NG2. Despite the fact that NG2 has been implicated in control of OPC migration, its mode of action remains unknown. Here, we show in vitro and in vivo that NG2 controls migration of OPC through the regulation of cell polarity. In stab wounds in adult mice we show that NG2 controls orientation of OPC toward the wound. NG2 stimulates RhoA activity at the cell periphery via the MUPP1/Syx1 signaling pathway, which favors the bipolar shape of migrating OPC and thus directional migration. Upon phosphorylation of Thr-2256, downstream signaling of NG2 switches from RhoA to Rac stimulation. This triggers process outgrowth through regulators of front-rear polarity and we show using a phospho-mimetic form of NG2 that indeed NG2 recruits proteins of the CRB and the PAR polarity complexes to stimulate Rac activity via the GEF Tiam1. Our findings demonstrate that NG2 is a core organizer of Rho GTPase activity and localization in the cell, which controls OPC polarity and directional migration. This work also reveals CRB and PAR polarity complexes as new effectors of NG2 signaling in the establishment of front-rear polarity.
authors.affiliation: Molecular Cell Biology, Department of Biology, Johannes Gutenberg University of Mainz, D-55122 Mainz, Germany. biname@uni-mainz.de
authors.forename: Fabien
authors.initials: F
authors.lastname: Binamé
authors.forename: Dominik
authors.initials: D
authors.lastname: Sakry
authors.forename: Leda
authors.initials: L
authors.lastname: Dimou
authors.forename: Valérie
authors.initials: V
authors.lastname: Jolivel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trotter
mesh_terms: D000941:Antigens / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D048430:Cell Shape / Q000235:genetics / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D010766:Phosphorylation; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013234:Stem Cells; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D013912:Threonine / Q000378:metabolism; D062725:Tight Junction Proteins / Q000235:genetics / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D012313:RNA; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D013912:Threonine; D062725:Tight Junction Proteins; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4; C107903:PATJ protein, human; C087334:TIAM1 protein, human